Sexual Health Assessment in Women with Lung Cancer study: Sexual health assessment in women with lung cancer.

BACKGROUND: Sexual health is understudied and underreported in patients with lung cancer, and most data precede the approval of widely used targeted therapies and immune checkpoint inhibitors. The authors sought to evaluate the prevalence of sexual dysfunction in women with lung cancer in our current clinical environment. METHODS: This cross-sectional survey study was administered online to 249 women via the GO2 for Lung Cancer (GO2) Registry, using the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Measures questionnaire. Participants were recruited between June 2020 to June 2021. Eligibility criteria included age >18 years, self-identifying as a woman, fluency in English, and a lung cancer diagnosis within 10 years. RESULTS: Most (67%) had stage IV lung cancer and 47% were receiving targeted therapy; 66% were undergoing active treatment. Despite 54% of participants reporting "recent" sexual activity, most (77%) indicated having little to no interest in sexual activity and 48% reported recent minimal satisfaction with their sex life. The most common reasons negatively affecting participants' satisfaction with their sex life included fatigue (40%) and feeling sad/unhappy (28%). Common reasons for lack of recent sexual activity included lack of interest (68%) and vaginal dryness or pain (30%). Compared to pre-diagnosis, women were significantly less likely to have recent interest in sexual activity. In multivariable logistic-regression, vaginal dryness showed a significant negative association with recent interest in sexual activity. CONCLUSIONS: Sexual dysfunction is prevalent in women with lung cancer. Sexual health should be integrated into routine care for patients with lung cancer.

Genomic Characterization of Aggressive Breast Cancer in Younger Women.

PURPOSE: Although breast cancer (BC) risk increases with age, BC in younger women is more aggressive with higher mortality compared with older women. We characterize the genomic landscape of BCs in younger women. METHODS: Clinicopathologic, molecular, and genomic differences across age groups (< 40 years, 40-60 years, > 60 years) in female BC patients were investigated in two large cohorts [AACR-GENIE8.1 (n = 11,594) and METABRIC (n = 2509)]. Cox-proportional regression analyzed the prognostic impact of age groups for disease-specific survival (DSS) and recurrence-free survival (RFS) in METABRIC and progression-free survival (PFS) in GENIE cohorts. Chi-squared test was used to assess statistical associations between genomic alterations and age groups. RESULTS: Survival analysis showed that women < 40 years had shorter DSS [hazard ratio (HR): 1.52, p = 0.005], RFS (HR: 1.4, p = 0.006), and PFS (HR: 1.82, p = 0.0003) compared with women 40-60 years, and shorter RFS (HR: 1.5, p = 0.001) and PFS (HR: 2.95, p < 0.0001) compared with women > 60 years. Molecular subtypes in the METABRIC cohort showed women < 40 years were enriched with basal, and HER2+ subtypes, and less enriched with luminal A and B subtype (p < 0.0001). Characterization of genomic alterations in both cohorts demonstrated that BCs in women < 40 years were more enriched with TP53 mutations (FDR < 0.0001), BRCA1 mutations (FDR = 0.01), ERBB2 amplifications (FDR < 0.001), CDK12 amplifications (FDR < 0.001), and PPM1D amplifications (FDR < 0.001). In contrast, BCs in older women (> 60 years) were more enriched with PIK3CA, KMT2C, and CDH1 mutations (FDR < 0.0001). CONCLUSIONS: BCs in young women are associated with shorter survival and more aggressive genomic features, including mutations in TP53 and BRCA1, and amplifications in ERBB2 and CDK12. These findings have the potential to impact clinical trial design and treatment.

Disparities in Primary Breast Cancer Stage at Presentation Among Hispanic Subgroups.

BACKGROUND: Although the United States (US) Hispanic population consists of diverse communities, prior breast cancer studies often analyze this group in aggregate. Our aim was to identify differences in breast cancer stage at presentation in the US population, with a particular focus on Hispanic subgroups. METHODS: Data from the National Cancer Database (NCDB) from 2004 to 2017 were used to select women with primary breast cancer; individuals were disaggregated by racial and ethnic subgroup and Hispanic country of origin. Ordinal logistic regression was used to create adjusted odds ratios (aORs) with 95% confidence intervals (CIs), with higher odds representing presentation at later-stage breast cancer. Subgroup analysis was conducted based on tumor receptor status. RESULTS: Overall, among 2,282,691 women (5.2% Hispanic), Hispanic women were more likely to live in low-income and low-educational attainment neighborhoods, and were also more likely to be uninsured. Hispanic women were also more likely to present at later-stage primary breast cancer when compared with non-Hispanic White women (aOR 1.19, 95% CI 1.18-1.21; p < 0.01). Stage disparities were demonstrated when populations were disaggregated by country of origin, particularly for Mexican women (aOR 1.55, 95% CI 1.51-1.60; p < 0.01). Disparities worsened among both racial and country of origin subgroups in women with triple-negative disease. CONCLUSION: Later breast cancer stage at presentation was observed among Hispanic populations when disaggregated by racial subgroup and country of origin. Socioeconomic disparities, as well as uncaptured disparities in access and/or differential care, may drive these observed differences. Future studies with disaggregated data are needed to characterize outcomes in Hispanic communities and develop targeted interventions.

Radiation oncology management of stage III and IVA cervical carcinoma.

Worldwide, stage III-IVA carcinomas of the uterine cervix comprise a significant proportion of cases at presentation, and have a higher rate of recurrence and worse overall survival. This review will discuss the epidemiology, prevention strategies, clinical presentation, and treatment recommendations for stage III-IVA cervical cancer. The focus will be on the role of radiation therapy, concurrent chemoradiotherapy, and brachytherapy, including the potential benefits and anticipated toxicities. The unique challenges and considerations of fistula formation and approaches to management will be highlighted, and follow-up care and future directions discussed. As low and middle income countries bear the highest burden of advanced stage carcinoma of the uterine cervix, this review will address the unique needs of global communities.

Prostate cancer incidence across stage, NCCN risk groups, and age before and after USPSTF Grade D recommendations against prostate-specific antigen screening in 2012.

BACKGROUND: We sought to determine the extent to which US Preventive Services Task Force (USPSTF) 2012 Grade D recommendations against prostate-specific antigen screening may have impacted recent prostate cancer disease incidence patterns in the United States across stage, National Comprehensive Cancer Network (NCCN) risk groups, and age groups. METHODS: SEER*Stat version 8.3.4 was used to calculate annual prostate cancer incidence rates from 2010 to 2015 for men aged ≥50 years according to American Joint Committee on Cancer stage at diagnosis (localized vs metastatic), NCCN risk group (low vs unfavorable [intermediate or high-risk]), and age group (50-74 years vs ≥75 years). Age-adjusted incidences per 100,000 persons with corresponding year-by-year incidence ratios (IRs) were calculated using the 2000 US Census population. RESULTS: From 2010 to 2015, the incidence (per 100,000 persons) of localized prostate cancer decreased from 195.4 to 131.9 (Ptrend  < .001) and from 189.0 to 123.4 (Ptrend  < .001) among men aged 50-74 and ≥75 years, respectively. The largest relative year-by-year decline occurred between 2011 and 2012 in NCCN low-risk disease (IR, 0.77 [0.75-0.79, P < .0001] and IR 0.68 [0.62-0.74, P < .0001] for men aged 50-74 and ≥75 years, respectively). From 2010-2015, the incidence of metastatic disease increased from 6.2 to 7.1 (Ptrend  < .001) and from 16.8 to 22.6 (Ptrend  < .001) among men aged 50-74 and ≥75 years, respectively. CONCLUSIONS: This report illustrates recent prostate cancer "reverse migration" away from indolent disease and toward more aggressive disease beginning in 2012. The incidence of localized disease declined across age groups from 2012 to 2015, with the greatest relative declines occurring in low-risk disease. Additionally, the incidence of distant metastatic disease increased gradually throughout the study period.

Conservative management of low-risk prostate cancer among young versus older men in the United States: Trends and outcomes from a novel national database.

BACKGROUND: Management for men aged ≤55 years with low-risk prostate cancer (LRPC) is debated given quality-of-life implications with definitive treatment versus the potential missed opportunity for cure with conservative management. The objective of this study was to define rates of conservative management for LRPC and associated short-term outcomes in young versus older men in the United States. METHODS: The nonpublic Surveillance, Epidemiology, and End Results Prostate with Active Surveillance/Watchful Waiting (AS/WW) Database identified 50,302 men who were diagnosed with LRPC from 2010 through 2015. AS/WW rates in the United States were stratified by age (≤55 vs ≥56 years). Prostate cancer-specific mortality and overall mortality were defined by initial management type (AS/WW vs definitive treatment [referent]) and age. RESULTS: AS/WW utilization increased from 8.61% (2010) to 34.56% (2015) among men aged ≤55 years (P for trend <0.001) and from 15.99% to 43.81% among men aged ≥56 years (P for trend <.001). Among patients who had ≤2 positive biopsy cores, AS/WW rates increased from 12.90% to 48.78% for men aged ≤55 years and from 21.85% to 58.01% for men aged ≥56 years. Among patients who had ≥3 positive biopsy cores, AS/WW rates increased from 3.89% to 22.45% for men aged ≤55 years and from 10.05% to 28.49% for men aged ≥56 years (all P for trend <.001). Five-year prostate cancer-specific mortality rates were <0.30% across age and initial management type subgroups. CONCLUSIONS: AS/WW rates quadrupled for patients aged ≤55 years from 2010 to 2015, with favorable short-term outcomes. These findings demonstrate the short-term safety and increasing acceptance of AS/WW for both younger and older patients. However, there are still higher absolute rates of AS/WW in older patients (P < .001), suggesting some national ambivalence toward AS/WW in younger patients.

Pilot Study Assessing Student Interest in Combined Residency Training Pathways With Radiation Oncology.

Purpose: Most medical students have limited exposure to radiation oncology (RO) before deciding which specialty to choose for residency. This may limit the number and diversity of RO applicants. The purpose of this study was to determine students' views on a combined pathway program of RO with internal medicine (IM), as well as other related medical specialties, as a potential means of overcoming barriers to interest in RO and the early decision point to solo training in a highly specialized field. Methods and Materials: In July to August 2022, all 299 United States student and postgraduate year 1 members of the American Society for Radiation Oncology were sent an electronic survey assessing their views on advantages and disadvantages of a combined IM/RO training pathway, and interest in several options of combined pathway programs. Results: Eighty participants completed the survey (response rate 27%). Thirty-four (43%) were very or extremely interested in IM/RO residency (median Likert-type rating 3, IQR 2-4). The most important potential advantages of an IM/RO pathway included greater flexibility in employment options (n = 51, 64%), enhanced general medical knowledge to facilitate ambitions in other career pathways (n = 46, 58%), improved patient care (n = 43, 54%), and having a pathway for combined hematologic/oncology and RO board certification (n = 46, 58%). In comparison to IM/RO, participants were significantly more interested in a combined RO and hematology/oncology program (median Likert-type rating 5, IQR 5-5, P = .005). Among the subgroup of 26 survey participants who believed it less likely they would apply for RO residency, 18 (69%) thought an IM/RO pathway would increase their interest in RO (median Likert-type rating 4, IQR 3-5). Interest in IM/RO did not differ by gender, race, or ethnicity. Conclusions: Combined training pathways involving RO were viewed positively by survey respondents, and may be particularly appealing to those less committed to a career in RO. Further research will help guide recommendations for the creation of these programs.

A Multi-Institutional Survey of Radiation Oncology Professionals' Knowledge, Attitudes, and Practice Behaviors Toward Sexual and Gender Minority Patients With Cancer.

Purpose: Sexual and gender minority (SGM) individuals have an increased risk of poor health outcomes, in part due to knowledge and training gaps in health care education. This study sought to evaluate the knowledge, attitudes, and practice behaviors of various health care role groups within radiation oncology toward SGM patients. Methods and Materials: A 38-item web-based survey was emailed to 1045 staff across 2 large radiation oncology departments. The survey assessed demographics, attitudes, knowledge, and practice behaviors. χ2 tests were performed to explore differences in survey responses by age, political affiliation, religious identity, year since graduation, and role groups. One-way analysis of variance tests were conducted to determine differences between respondents' confidence in knowledge and performance on the knowledge section of the survey. Thematic analysis was applied to the open discussion section. Results: Of the 223 respondents, 103 clinicians (physicians/advanced practice providers/nurses) and 120 nonclinicians (administrative staff, medical assistants, and other nonmedical staff) participated in the survey (21.3% response rate): 72.6% answered the knowledge questions; 93.5% stated they were comfortable treating sexual minorities, or lesbian, gay, bisexual, and queer + patients; 88% indicated comfort in treating transgender patients; 36.6% stated they were confident in their knowledge of the health needs of transgender patients; and 50.3% expressed confidence in treating lesbian, gay, bisexual, and queer + patients. Fewer nonclinicians than clinicians thought that gender identity, sexual orientation, and sex assigned at birth were important to provide the best care (P < .05). The open comments section identified key themes, including the belief that current educational tools are not helpful, desire for more educational formats (lectures, case-based learning, seminars), and an overall interest in SGM health education. Conclusions: Most staff feel comfortable in treating SGM patients but are less confident in the distinct needs of this population. Knowledge gaps persist for both clinicians and nonclinicians, indicating a need for further training specific to oncology care.

Disparities in Stage at Presentation Among Hispanic and Latinx Patients With Non-Small-Cell Lung Cancer in the United States.

PURPOSE: Hispanic and Latinx people in the United States are the fastest-growing ethnic group. However, previous studies in non-small-cell lung cancer (NSCLC) often analyze these diverse communities in aggregate. We aimed to identify differences in NSCLC stage at diagnosis in the US population, focusing on disaggregated Hispanic/Latinx individuals. METHODS: Data from the National Cancer Database from 2004 to 2018 identified patients with primary NSCLC. Individuals were disaggregated by racial and ethnic subgroup and Hispanic country of origin. Ordinal logistic regression adjusting for age, facility type, income, educational attainment, comorbidity index, insurance, and year of diagnosis was used to create adjusted odds ratios (aORs), with higher odds representing diagnosis at later-stage NSCLC. RESULTS: Of 1,565,159 patients with NSCLC, 46,616 were Hispanic/Latinx (3.0%). When analyzed in the setting of race and ethnicity, Hispanic patients were more likely to be diagnosed with metastatic disease compared with non-Hispanic White (NHW) patients: 47.0% for Hispanic Black, 46.0% Hispanic White, and 44.3% of Hispanic other patients versus 39.1% of non-Hispanic White patients (P < .001 for all). By country of origin, 51.4% of Mexican, 41.7% of Puerto Rican, 44.6% of Cuban, 50.8% of South or Central American, 48.4% of Dominican, and 45.6% of other Hispanic patients were diagnosed with metastatic disease, compared with 39.1% of NHWs. Conversely, 20.2% of Mexican, 26.9% of Puerto Rican, 24.2% of Cuban, 22.5% of South or Central American, 23.7% of Dominican, and 24.5% of other Hispanic patients were diagnosed with stage I disease, compared with 30.0% of NHWs. All Hispanic groups were more likely to present with later-stage NSCLC than NHW patients (greatest odds for Mexican patients, aOR, 1.44; P < .001). CONCLUSION: Hispanic/Latinx patients with non-small-cell lung cancer were more likely to be diagnosed with advanced disease compared with NHWs. Disparities persisted upon disaggregation by both race and country of origin, with over half of Mexican patients with metastatic disease at diagnosis. Disparities among Hispanic/Latinx groups by race and by country of origin highlight the shortcomings of treating these groups as a monolith and underscore the need for disaggregated research and targeted interventions.

Large language models to identify social determinants of health in electronic health records.

Social determinants of health (SDoH) play a critical role in patient outcomes, yet their documentation is often missing or incomplete in the structured data of electronic health records (EHRs). Large language models (LLMs) could enable high-throughput extraction of SDoH from the EHR to support research and clinical care. However, class imbalance and data limitations present challenges for this sparsely documented yet critical information. Here, we investigated the optimal methods for using LLMs to extract six SDoH categories from narrative text in the EHR: employment, housing, transportation, parental status, relationship, and social support. The best-performing models were fine-tuned Flan-T5 XL for any SDoH mentions (macro-F1 0.71), and Flan-T5 XXL for adverse SDoH mentions (macro-F1 0.70). Adding LLM-generated synthetic data to training varied across models and architecture, but improved the performance of smaller Flan-T5 models (delta F1 + 0.12 to +0.23). Our best-fine-tuned models outperformed zero- and few-shot performance of ChatGPT-family models in the zero- and few-shot setting, except GPT4 with 10-shot prompting for adverse SDoH. Fine-tuned models were less likely than ChatGPT to change their prediction when race/ethnicity and gender descriptors were added to the text, suggesting less algorithmic bias (p < 0.05). Our models identified 93.8% of patients with adverse SDoH, while ICD-10 codes captured 2.0%. These results demonstrate the potential of LLMs in improving real-world evidence on SDoH and assisting in identifying patients who could benefit from resource support.

Spanish Adaptation and Evaluation of Clinical Discussion Guides: Communicating the External Beam Radiotherapy Experience (CEBRE) en Español.

PURPOSE: Cancer is the leading cause of death for the Hispanic/Latinx United States (US) community, which comprises 64% of the US population with limited English proficiency. Despite the common use of radiation therapy for cancer treatment, there is a dearth of radiation therapy educational materials-at appropriate reading levels-available in Spanish. To address the gap in patient-centered educational resources for communicating with Spanish-speaking patients about radiation therapy, we sought to linguistically and culturally adapt the Communicating the External Beam Radiotherapy Experience (CEBRE) clinical discussion guide series into Spanish. METHODS AND MATERIALS: From January to December 2021, we developed and applied a stepwise methodology for Spanish adaptation of the discussion guides involving (1) professional translation; (2) interprofessional review for linguistic and cultural appropriateness and medical accuracy; (3) design review; and (4) evaluation for readability, understandability, and actionability using validated tools. We applied 4 indices for readability evaluation: Gilliam-Peña-Mountain, Läsbarhetsindex, Rate Index, and the Spanish Simple Measure of Gobbledygook. Two trained reviewers assessed understandability and actionability using the Patient Education Materials Assessment Tool. RESULTS: After 2 revision rounds, 4 CEBRE en español discussion guides were produced through an interprofessional, iterative translation and linguistic/cultural adaptation process. Readability scores across the 4 guides ranged from 4.3 to 7.3 grade-level equivalents, thereby meeting the American Medical Association's 8th-grade standard. Patient Education Materials Assessment Tool analysis yielded near-perfect scores along understandability and actionability domains. CONCLUSIONS: The stepwise linguistic/cultural adaptation process yielded a patient-centered guide that is appropriately readable, understandable, and actionable for Spanish-speaking patients receiving radiation therapy in the US. Future work should include an external evaluation of CEBRE en español by clinicians and patients. The methodology described can be applied to adapting resources for patient-centered communication in other fields of medicine and into other languages as part of an interprofessional approach to delivering equitable health care for all.

Localized prostate cancer disparities in risk group at presentation and access to treatment for Hispanic men.

BACKGROUND: Despite great heterogeneity amongst Hispanic groups, prostate cancer studies often report Hispanic patients in aggregate. We sought to identify differences in prostate cancer risk group at presentation and treatment status among Hispanic subgroup populations. METHODS: Patients with localized prostate adenocarcinoma diagnosed from 2004-2017 were identified in the National Cancer Database (NCDB) and disaggregated by racial subgroup and Hispanic country of origin. Ordinal logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment with intermediate-unfavorable or high-risk disease. RESULTS: In our sample (n = 895,087), Hispanic men had greater odds of presenting with higher-risk localized prostate cancer compared with non-Hispanic White men (AOR = 1.18 95% CI 1.16-1.21, p < 0.001). Additionally, Hispanic Black men were less likely to present with higher-risk disease than non-Hispanic Black men. Disparities also existed when disaggregated by country of origin, particularly for Mexican men. Amongst men with unfavorable-risk disease, Hispanic men were less likely to receive treatment than non-Hispanic White men (95% CI 0.57-0.67, p < 0.001). The odds of Hispanic Black patients receiving treatment was 2.00 times the odds (95% CI 1.17-3.41 p = 0.011) of non-Hispanic Black patients receiving treatment. Upon disaggregation by country of origin, disparities persisted, particularly for Mexican men. CONCLUSION: We found marked heterogeneity when risk group at presentation and treatment for higher-risk disease were disaggregated by racial subgroup and country of origin. Our findings support further collection of disaggregated data in Hispanic communities and study of potential mechanisms underlying the observed differences.

Chromosome 8q arm overexpression is associated with worse prostate cancer prognosis.

OBJECTIVE: Chromosome 8q arm (chr8q) is the most amplified chromosomal segment in advanced metastatic castration-resistant prostate cancer after chXq12. These regions harbor important oncogenes driving prostate cancer progression, including MYC that plays a role in various hallmarks of cancer, including cell cycle progression and immune surveillance. Herein we characterize the co-expression patterns of chr8q genes and their clinical utility in more than 7,000 radical prostatectomy samples. MATERIALS AND METHODS: Copy Number alterations of 336 genes on chr8q21 to chr8q24 were extracted from 2 primary prostate cancer cohorts (TCGA, n = 492; MSK-primary, n = 856) and 3 metastatic prostate cancer cohorts (MSK-met, N = 432; MSK-mCSPC, N = 424; SU2CPNAS, n = 444) from cBioPortal. Expression data for the 336 genes was extracted from 6,135 radical prostatectomy samples from Decipher GRID registry. For survival analysis, patients were grouped into top 10% and top 25% by band expression and were compared with the remaining cohort. Hazard ratios were calculated using Cox proportional hazards models. RESULTS: Genes on chr8q were highly co-amplified and co-expressed. Copy number alterations and overexpression of chr8q genes in primary disease were associated with higher Gleason scores, increased risk of metastases, and increased prostate cancer specific mortality. Additionally, our data demonstrated high expression of MYC alone was not associated with differences in metastases free survival while high expression of other chr8q bands was associated with decreased metastases free survival. By combining chr8q data with an established genomic classifier like Decipher, we were able to develop a new model that was better at predicting metastases than Decipher alone. CONCLUSIONS: Our findings highlight the clinical utility of chr8q data, which can be used to improve prognostication and risk prediction in localized prostate cancer.